Chemotherapeutic Interaction of Vernonia amygdalina (Delile) Leaf Extract with Artesunate and Amodiaquine in Murine Malaria Model

Main Article Content

Esthinsheen Osirim
Oluwole I. Adeyemi
Sharon I. Igbinoba
Cyprian O. Onyeji

Abstract

Aim of the Study: Conventional antimalarial drugs are used concurrently with herbal remedies in malarial endemic developing countries. Vernonia amygdalina is one of such popular herbs used in the treatment of malaria. This study aimed at investigating the antimalarial chemotherapeutic interaction of Vernonia amygdalina (VA) when combined with Amodiaquine (AQ) and/or Artesunate (AS) in a murine Plasmodium berghei malaria model.

Methodology: Various doses of aqueous VA leaf extract (100-500 mg/kg/day), AQ (2-10 mg/kg/day) and AS (0.8-4 mg/kg/day) were administered orally to P berghei.-infected Swiss albino mice to determine their sub-therapeutic doses. These doses were subsequently used to investigate the chemotherapeutic interactions of VA with AQ and/or AS in both early and established malaria infection test models. The survival of animals with established infections that received different drug/herb treatments were determined using their mean survival time (days) and Kaplan-Meier survival curves (percentage). Using GraphPad Instat (version 3.10) and PrismR (version 5.01) the data obtained were subjected to One-way ANOVA, followed by Student-Newman-Keuls test. P < .05 was considered statistically significant.

Results: The sub-therapeutic doses of VA, AQ and AS were found to be 100 mg/kg, 2 mg/kg and 2.4 mg/kg, respectively. The chemosuppressive effect of AQ or AS was significantly increased (p< 0.05) when administered in combination with the VA extract. Similarly, combination of VA extract with AQ or AS resulted in significant (P < .05) parasite clearance when compared to the effects of the herb or the conventional drugs administered separately. The mean survival period of animals with established infection was also significantly enhanced by the VA alone or with AQ (or AS) compared to placebo.

Keywords:
Chemotherapeutic interaction, Murine malaria model, Vernonia amygdalina, artesunate

Article Details

How to Cite
Osirim, E., Adeyemi, O. I., Igbinoba, S. I., & Onyeji, C. O. (2020). Chemotherapeutic Interaction of Vernonia amygdalina (Delile) Leaf Extract with Artesunate and Amodiaquine in Murine Malaria Model. Journal of Pharmaceutical Research International, 32(3), 15-24. https://doi.org/10.9734/jpri/2020/v32i330410
Section
Original Research Article

References

World malaria report. World health organisation. Geneva; 2018.
(Accessed on 5, May, 2019)
Available:http://www.who.int/malaria/publications/world-malaria-report-2018/en/

World Health Organization. Malaria parasite counting. World health organisation; 2016.

Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning J, et al. Artemisinin resistance in Plasmodium falciparum malaria. The New England Journal of Medicine. 2009; 361:455-467.

Bhat GP, Surolia N. In vitro antimalarial activity of extracts of three plants used in the traditional medicine of India. American Journal of Tropical Medicine and Hygiene, 2001;65(4):304-308.

Sha A, Oguche S, Watila I, Ikpa T. In vitro antimalarial activity of the extracts of Vernonia amygdalina commonly used in traditional medicine in Nigeria. Science World Journal. 2011;6(2):5–9.

Willcox ML, Bodeker G. Traditional herbal medicines for malaria. British Medical Journal. 2004;329(7475):1156-1159.
Available:https://doi.org/10.1136/bmj.329.7475.1156

Ijeh I, Ejike CECC. Current perspectives on the medicinal potentials of Vernonia amygdalina Del. Journal of Medicinal Plants Research. 2011;5(7):1051–1061.

Masaba SC. The antimalarial activity of Vernonia amygdalina Del. (Compositae). Transactions Royal Society of Tropical Medicine and Hygiene. 2000;94:694-695.

Abosi AO, Raseroka BH. In vivo antimalarial activity of Vernonia amygdalina. British Journal of Biomedical Science. 2003;60(2):89–91.

Tona L, Cimanga RK, Mesia K, Musuamba CT, De Bruyne T, Apers S, Hernans N, Van Miert S, Pieters L, Totté J, Vlietinck AJ. In vitro antiplasmodial activity of extracts and fractions of seven medicinal plants used in the Democratic Republic of Congo. Journal of Ethnopharmacology. 2004;93:27-32.

Challand S, Willcox MA. Clinical trial of the traditional medicine Vernonia amygdalina in the treatment of uncomplicated malaria. The Journal of Alternative and Complementary Medicine. 2009;15(11): 1231–1237.

Onyeji CO, Igbinoba SI, Olayiwola G, Adehin A. Insight into clinically effective herbal antimalarial products: Effects on drug metabolizing enzymes and p-glycoprotein. African Journal of Pharmacy and Pharmacology. 2017;12(48):591-613.

Adibe MO. Prevalence of concurrent use of herbal and synthetic medicines among outpatients in a mission hospital in Nigeria. International Journal of Drug Development and Research. 2009;1(1):60-66.

NIH. Guidelines for the care and use of laboratory animals. National Academic Press, NIH Publication. 1996;85:23.

Anagu OL, Attama AA, Okore VC, Gugu HT, Ngene AA, Esimone CO. Azadirachta indica extract-artesunic acid combination produces an increased cure rate of Plasmodium berghei-infected mice. Pharmaceutical Biology. 2014;52:883–889.

O’Connell KE, Mikkola AM, Stepanek AM, Vernet A, Hall CD, Sun CC, Brown DE. Practical murine hematopathology: A comparative review and implications for research. Comparative Medicine. 2015;65 (2):96–113.

Ryley JF, Peters W. The antimalarial activity of some quinoline esters. Annals of Tropical Medicine and Parasitology. 1970;64(2).

Fasinu PS, Bouic PJ, Rosenkranz B. An overview of the evidence mechanisms of herb-drug interactions. Frontiers in Pharmacology. 2012;3:1–19.

Mackinnon MJ, Gaffney DJ, Read AF. Virulence in rodent malaria: Host genotype by parasite genotype interactions. Infection, Genetics and Evolution. 2002;1: 287-296

Adepiti AO, Elujoba AA, Bolaji OO. Evaluation of herbal antimalarial MAMA decoction-amodiaquine combination in murine malaria model. Pharmaceutical Biology. 2016;0209(54:10):2298–2303.

World Health Organization. Guidelines for the treatment of malaria. World Health Organization, Geneva, Switzerland; 2015.

Iwalokun BA. Enhanced antimalarial effects of chloroquine by aqueous Vernonia amygdalina leaf extract in mice infected with chloroquine resistant and sensitive Plasmodium berghei strains. African Health Sciences. 2008;8(1):25–35.

Sirima SB, Gansané A. Artesunate–amodiaquine for the treatment of uncomplicated malaria. Expert Opinion on Investigational Drugs. 2007;16(7):1079-1085

Oyindamola OA, Nekabari G, Grace OG. Lopinavir/ritonavir enhanced the antimalarial activity of amodiaquine and artesunate in a mouse model of Plasmodium berghei. Journal of Chemotherapy; 2016.
DOI: 10.1080/1120009X.2016.1139770

de Oca MM, Engwerda C, Haque A. Plasmodium berghei ANKA (PbA) infection of C57BL/6J mice: A model of severe malaria. Methods Mol. Biol. 2013;103: 203– 213.

Franke-Fayard B, Janse CJ, Cunha-Rodrigues M, Ramesar J, Büscher P, Que I, Löwik C, Voshol PJ, den Boer MA, van Duinen SG, Febbraio M, Mota MM, Waters AP. Murine malaria parasite sequestration: CD36 is the major receptor, but cerebral pathology is unlinked to sequestration. Proc. Natl Acad. Sci. USA. 2005;102: 11468–11473.

De Niz M, Ullrich A, Heibert A, Soares AB, Pick C, Lyck R, Keller D, Kaiser G, Prado M, Flemming S, del Portillo H, Janse CJ Heussler V, Spielmann T. The machinery underlying malaria parasite virulence is conserved between rodent and human malaria parasites. Nature Communica-tions. 2016;7:11659.
DOI: 10.1038